Children and adolescents who take stimulants for attention-deficit hyperactivity disorder (ADHD) are at twice the risk of experiencing a cardiovascular event than children with ADHD not prescribed psychostimulants, according to a prospective study of more than 700,000 children in Denmark, 8,300 of whom had ADHD.
Researchers published their findings—which also showed a rare but statistically significant risk of cardiovascular events when children and adolescents without ADHD used stimulants—in the online Journal of Child and Adolescent Psychopharmacology.
"This study confirms the small but real risk we have understood for some time through prior reports and clinical experience," said the journal’s editor-in-chief Harold S. Koplewicz, MD, president of the Child Mind Institute, New York, NY. "But [this study’s] excellent design and the robust sample size make it abundantly clear that treating clinicians cannot ignore existing guidelines concerning the assessment of cardiac risk prior to treatment and monitoring key vital signs during the course."
The longitudinal study, which included all children born in Denmark between 1990 and 1999, had an observation period of 9.5 years. Of the study’s 714,258 participants, 5,734 experienced a cardiovascular event (84 events per 100,000 person-years), researchers reported.
Among the 8,300 children with ADHD, 111 cardiovascular events (170 events per 100,000 person-years) were identified.
Events in the ADHD population included arrhythmias (23%), cerebrovascular disease (9%), hypertension (8%), ischemic heart disease (2%), heart failure (2%), heart disease caused by rheumatic fever (2%), cardiac arrest (<1%), pulmonary heart disease (<1%), heart disease not otherwise specified (14%), and cardiovascular disease not otherwise specified (40%), according to the study.
Researchers also reported an important dose-response relationship between stimulants and cardiovascular events.
“Specifically, children prescribed >30 mg of methylphenidate per day 12 months prior to the event had a higher risk than children not in treatment,” researchers wrote. “In contrast, examining the dose at the time of the cardiovascular event, we found an inverse relationship between cardiovascular events and the current dose, with the highest risk in the group of children being prescribed the lowest dose.”
1. Dalsgaard S, Kvist AP, Leckman JF, Nielsen HS, Simonsen M. Cardiovascular safety of stimulants in children with attention-deficit/hyperactivity disorder: a nationwide prospective cohort study. Journal of Child and Adolescent Psychopharmacology. 2014 June 23. [Epub ahead of print].